Wrapping stem cells with wireless electrical nanopatches for traumatic brain injury therapy

 Do you really think your competent? doctor can see the benefits for stroke rehab and contact stroke leadership to get human research done? NO? So you don't believe you have a functioning stroke doctor; do you?  I don't care that there is NO stroke leadership anywhere! Your competent? doctor should band with other doctors to create a leadership structure.  Otherwise stroke will never be solved with NO leadership or strategy! Which is why survivors should be in charge, we would get things done.

Wrapping stem cells with wireless electrical nanopatches for traumatic brain injury therapy

• Liang Wang,
• Jingyi Du,
• Qilu Liu,
• Dongshuang Wang,
• Wenhan Wang,
• Ming Lei,
• Keyi Li,
• Yiwei Li,
• Aijun Hao,
• Yuanhua Sang,
• Fan Yi,
• Wenjuan Zhou,
• Hong Liu,
• Chuanbin Mao &
• Jichuan Qiu 

Nature Communications volume 15, Article number: 7223 (2024) Cite this article

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Abstract

Electrical stimulation holds promise for enhancing neuronal differentiation of neural stem cells to treat traumatic brain injury. However, once the stem cells leave the stimulating material and migrate post transplantation, electrical stimulation on them is diminished. Here, we wrap the stem cells with wireless electrical nanopatches, the conductive graphene nanosheets. Under electromagnetic induction, electrical stimulation can thus be applied in-situ to individual nanopatch-wrapped stem cells on demand, stimulating their neuronal differentiation through a MAPK/ERK signaling pathway. Consequently, 41% of the nanopatch-wrapped stem cells differentiate into functional neurons in 5 days, as opposed to only 16.3% of the unwrapped ones. The brain injury male mice implanted with the nanopatch-wrapped stem cells and exposed to a rotating magnetic field 30 min/day exhibit significant recovery of brain tissues, behaviors, and cognitions, within 28 days. This study opens up an avenue to individualized electrical stimulation of transplanted stem cells for treating neurodegenerative diseases.

Metformin protects against pericyte apoptosis and promotes neurogenesis through suppressing JNK p38 MAPK signalling activation in ischemia/reperfusion injury

WHOM is going to do the research on humans to see if this stops the pericytes strangling capillaries  piece of the neuronal cascade of death?

Metformin protects against pericyte apoptosis and promotes neurogenesis through suppressing JNK p38 MAPK signalling activation in ischemia/reperfusion injury

Author links open overlay panelChangLiu^aDiZhang^bZhengfangLu^bJiangMan^bZhenZhang^aXiaojuanFu^aKefeiCui^cJianpingWang^a

https://doi.org/10.1016/j.neulet.2022.136708Get rights and content

Highlights

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Metformin inhibited pericytes apoptosis contributing to promoting SVZ neurogenesis and neurologic outcome in tMCAO mice.

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Metformin supressed JNK p38 MAPK signalling activation in tMCAO mice which inhibited pericytes apoptosis.

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Anisomycin abolished neuroprotective effects of Metformin through activating JNK p38 MAPK signalling.

Abstract

Metformin (MET) has been the subject of many classic studies in possessing antiapoptotic, anti-inflammatory, antioxidation activities and antiviral. Recently investigators have examined the anti-apoptosis effects of MET in acute myocardial infarction and Intracerebral hemorrhage, but very little is currently known about how it regulates ischemic stroke-induced pericytes apoptosis and neural stem cells (NSCs) proliferation. The present research explored the potential neuroprotective mechanisms of MET using transient middle cerebral artery occlusion(tMCAO) mice. The experimental work presented that tMCAO mice treated by metformin had better neurologic outcomes on days 1, 3, and 7 after operation, and alleviated blood–brain barrier (BBB) destruction, brain water content and infarct volume on 72 h after surgery. The data showed that MET alleviated BBB disruption by reducing PDGFRβ/ matrix metalloproteinase-9 (MMP9) positive cells, relieving zonula occludens-1 (ZO-1) drop away and increasing pericyte coverage through remarkably reducing the percentage of PDGFRβ/caspase-3 positive cells. In addition, MET induced antiapoptotic activity followed by downregulating cleaved caspase-3 and Bax expression. Moreover, JNK signaling pathway has been proved to be pivotal in mediating apoptosis in cerebral ischemia/reperfusion (I/R) injury. The results of this research illustrated that MET treatment downregulated the levels of phosphorylated JNK and P38 in vivo, however the use of JNK activator anisomycin (ANI) could reverse the neuroprotection effect of MET, demonstrating that the JNK pathway is associated with the anti-apoptosis mechanisms of MET. Finally, metformin remarkably increased the percentage of BrdU/DCX-positive cells in subventricular zone (SVZ) and up-regulated BDNF、VEGF and NGF expression after ischemia/reperfusion(I/R) injury on day 7. Our data illustrated that metformin provides an effective therapy for I/R injury.

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Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

Someplace in all these big words is some useful information to be acted upon, which will never occur.  You put an RFP out to researchers, pay for it with foundation grants and write the results up in a stroke protocol available in a public database. 

Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance   

Ján Lehotský^1*, Barbara Tothová¹, Maria Kovalská^1,2, Dušan Dobrota¹, Anna Beňová¹, Dagmar Kalenská¹ and Peter Kaplán¹

• ¹Institute of Medical Biochemistry and BioMed, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
• ²Institute of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia

Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic tolerance and recognition of the co-morbid risk factors would result in development of new avenues for exploration of novel therapeutics against ischemia and stroke.

Introduction

Many experimental and clinical studies provide evidence that co-morbid disorders are potential risk factors for development of vascular disorders in humans including stroke (Lehotský et al., 2009a; Kwon et al., 2014). At present, there are several known factors elevating the risk of ischemic stroke which include transient ischemic attack (TIA), arterial diseases, atrial fibrillation, improper diet and/or obesity and physical inactivity (Dirnagl et al., 2009). As it has been verified by many studies, even mild hyperhomocysteinemia (hHcy) may increase the risk for clinical manifestations of stroke, probably due to the pleiotropic biochemical properties of homocysteine (Hcy) and its impact on venous and arterial atherosclerotic modifications (Refsum et al., 1998; Steele et al., 2013; Kwon et al., 2014; Petras et al., 2014; Williams et al., 2014). In fact, Hcy suppresses NO production by endothelial cells and platelets and increases generation of reactive oxygen species (ROS) by the release of arachidonic acid from the platelets. It also inhibits glutathione peroxidase and thus stimulates proliferation of endothelial cells (see Petras et al., 2014, for review). In addition, Hcy has been shown to inhibit methyltransferases, to suppress DNA repair and to facilitate apoptosis when accumulated inside the cells. Autooxidation of Hcy metabolites results in H₂0₂ accumulation (Boldyrev et al., 2013) and challlenging neurons to Hcy metabolites for longer period leads to necrotic cell death (Ziemińska et al., 2003). Clinical studies suggest that elevated homocysteine level frequently parallels progressive aging as well as neurodegenerative and acute disorders of the CNS, e.g., Alzheimer's disease or Parkinson's disease (Dionisio et al., 2010). Designing appropriate animal models relevant to the clinical conditions of human stroke is an important step for studying the disease ethiology. Until now, only sparse studies have been developed to explore the mutual effect of HCy and ischemic preconditioning (IPC) in animal models of ischemic stroke.

In this paper we summarize current overview on homocysteine conversion steps in the organism and present the genetic and metabolic causes of hyperhomocysteinemia-related neurotoxicity. Based on the results from our laboratory, we also document, in this context, that mutual effect of experimental hyperhomocysteinemia (hHCy) and ischemic insult with or without pre-ischemic challenge can have different outcomes on the extent of neuronal degeneration as well as on the intracellular signaling pathways leading to the preconditioning phenomenon.

More at link.

Understanding the protective effects of wine components and their metabolites in the brain function

They don't seem to have considered that only certain people can process alcohol healthily.

Moderate Drinking is Healthy Only for Some People

Understanding the protective effects of wine components and their metabolites in the brain function

¹ Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM. Nicolás Cabrera, 9, 28049 Madrid, Spain
² Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights Campus RG6 6AP, Reading, UK

^a e-mail: victoria.moreno@csic.es

Abstract

Moderate wine consumption has been suggested to exert a positive effect in prevention of neurodegenerative process and cognitive impairment. With the ultimate aim of achieving a better understanding of the molecular mechanisms behind this benefit, we have investigated the role of certain wine- derived phenolic metabolites and aroma compounds in the MAPK cascade (including ERK1/2, p38), one of the routes directly related to inflammation in neuronal cells. Some of the tested phenolic compounds, especially in the case of 3,4-dihydroxyphenylacetic acid, showed a significant neuroprotective effect against SIN-1-induced neuronal death. Regarding their effect over MAPK phosphorylation, inmunoblotting technique revealed a beneficial and significant decrease on the phosphorylation of p38 and ERK1/2 kinases after incubation with wine constituents. In addition, activity of caspase3-like protease, an executor of neuronal apoptosis and a downstream signal of MAPK, was significantly diminished by 3-(3-hydroxyphenyl) propionic acid and linalool, counterbalancing the increase produced by SIN-1. Altogether, these results suggest that wine aroma, phenolic compounds and their gut metabolites could exert neuroprotective actions by modulating MAPK signalling and caspase-3 proteases activation, which are known to play a key role in oxidative/ nitrosative stress-induced response.
© The Authors, published by EDP Sciences 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/).

Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals

I think this is more proof that coffee slows down the progression of dementia. But what the hell do I know? Your doctor is supposed to know all this stuff so ask her/him.
http://www.sciencedirect.com/science/article/pii/S0027510708002595

• Eun Sun Cho^{a, 1},
• Young Jin Jang^{a, 1},
• Mun Kyung Hwang^{a, b},
• Nam Joo Kang^{a, b},
• Ki Won Lee^{b, ,} ,
• Hyong Joo Lee^{a, ,}

• ^a Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea
• ^b Department of Bioscience and Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea

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Abstract

Neurodegenerative disorders such as Alzheimer's disease (AD) are strongly associated with oxidative stress, which is induced by reactive oxygen species (ROS) including hydrogen peroxide (H₂O₂). Recent studies suggest that moderate coffee consumption may reduce the risk of neurodegenerative diseases such as AD, but the molecular mechanisms underlying this effect remain to be clarified. In this study, we investigated the protective effects of chlorogenic acid (5-O-caffeoylquinic acid; CGA), a major phenolic phytochemical found in instant decaffeinated coffee (IDC), and IDC against oxidative PC12 neuronal cell death. IDC (1 and 5 μg/ml) or CGA (1 and 5 μM) attenuated H₂O₂-induced PC12 cell death. H₂O₂-induced nuclear condensation and DNA fragmentation were strongly inhibited by pretreatment with IDC or CGA. Pretreatment with IDC or CGA also inhibited the H₂O₂-induced cleavage of poly(ADP-ribose) polymerase (PARP), and downregulation of Bcl-X_L and caspase-3. The accumulation of intracellular ROS in H₂O₂-treated PC12 cells was dose-dependently diminished by IDC or CGA. The activation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) by H₂O₂ in PC12 cells was also inhibited by IDC or CGA. Collectively, these results indicate that IDC and CGA protect PC12 cells from H₂O₂-induced apoptosis by blocking the accumulation of intracellular ROS and the activation of MAPKs.

Paeoniflorin Protects against Ischemia-Induced Brain Damages in Rats via Inhibiting MAPKs/NF-κB-Mediated Inflammatory Responses

More hyperacute therapy to test in humans. 

Paeoniflorin Protects against Ischemia-Induced Brain Damages in Rats via Inhibiting MAPKs/NF-κB-Mediated Inflammatory Responses

Abstract Top

Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX₂ and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

Effect of 710nm Visible Light Irradiation on Neurite Outgrowth in Primary Rat Cortical Neurons following Ischemic Insult

Not sure that this really helps us at all  Meaning of In vitro (Latin: within glass) refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological contex.  In vivo is what we need.  Can't quite figure out how this would be done to live humans.
 http://www.sciencedirect.com/science/article/pii/S0006291X12008364

Abstract

Objective

We previously reported that 710nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model.

Materials &methods

Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm² and 50 mW/cm²) were given once to four times within 8 hours at 2 hr intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axiovision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting.

Results

Images captured after MAP2 immunocytochemistry showed significant (p<0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p < 0.05).

Conclusion

Our data suggest that LED treatment may promote synaptogenesis through MAPK activation and subsequently protect cell death in the in vitro stroke model.

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Highlights

► 710nm wavelength light (LED) has a protective effect in the stroke animal model. ► We determined the effects of LED irradiation in vitro stroke model. ► LED treatment promotes the neurite outgrowth through MAPK activation. ► The level of synaptic markers significantly increased with LED treatment. ► LED treatment protects cell death in the in vitro stroke model.